The current research proposal will be an in-depth investigation of the ability of the myocardium to respond to digoxin during conditions similar to those seen clinically in patients with varying forms of cardiac disease. The experiments outlined in this proposal will observe the inotropic effects and myocardial content of digoxin in either isolated cat papillary muscles or intact dog heart. Observations will be made on the ability of digoxin to exert an inotropic effect during alterations of tissue oxygen consumption, during electrolyte disturbances, during acid-base imbalances, or during myocardial ischemia or infarction. Many of the experiments in the intact dog heart model will employ a myocardial biopsy techniques so that the time course of myocardial up-take of digoxin, both during control conditions and under the influence of various experimental inervention, can be determined. In the ischemia studies, regional contractility of discrete areas of the myocardium will be recorded and correlated with regional myocardial digoxin content in the same areas. These studies will thus provide useful information about the inotropic effects of digoxin and the ability of the myocardium to bind digoxin. Since all studies outlined in the proposal will monitor not only the inotropic effect of digoxin but cardiac muscle content as well, circumstances can be identifed in which disparities exist between content and inotropic effect. Further, in the intact dog studies serum digoxin levels will be measured and compared to myocardial digoxin levels to determine serum:tissue ratios in the various conditions.